The etiology and pathogenesis of acute and chronic bacterial prostatitis and chronic abacterial prostatitis will be investigated in dogs. The factors influencing the excretion of antimicrobial substances in the prostatic fluid and tissue (lipid solubility, pKa and protein binding) will be systematically investigated and their relative importance defined. The experimental findings will be followed by clinical studies: I. Experimental Studies: E. coli 06 will be injected into the isolated prostatic artery of dogs to create bacterial prostatitis and tritiated lipid-A (the toxic factor in E. coli) will be injected into the prostatic artery, thus creating an abacterial, chronic prostatitis. This development will be followed histologically and the lipid-A localization determined by autoradiography. Prostatic secretion and interstitial prostatic tissue fluid obtained from tissue chambers implanted into the prostate in these two groups of dogs and in a control group will be obtained following administration of pilocarpine. Emphasis will be placed on culturing the secretion, measurement of pH and zinc content as well as the concentration of antimicrobial substances with varying lipid solubility, pKa and protein binding when administered by constant intravenous infusion. II. Clinical Studies: Prostatic tissue will be obtained from patients undergoing prostatectomy for benign hyperplasia with and without concomitant chronic prostatitis. Preoperatively the patients will receive antimicrobial substances which (based on above dog studies) would be expected to concentrate in prostatic fluid and tissue such as lipid soluble penicillin esters and macrolides such as erythromycin with a high pKa, lipid soluble chemotherapeutic agents with high pKa such as trimethoprim, and cephalosporins with low serum protein binding. These drugs will also be investigated in prostatic fluid of patients and in treatment of prostatitis. The results should provide guidelines for therapy of bacterial prostatitis.